In this application we propose the establishment of the University of Pennsylvania Prevention Clinical Trials Unit. Building upon a 12 year history of successful involvement in NIAID funded Networks (Project Jumpstart, HIVNET, and HPTN) we are applying for collaborations with three of the proposed leadership groups: Vaccines, HPTN, and Microbicides. Reflecting this connection to existing networks we are submitting transition budgets for three ongoing NIAID sponsored clinical trials: HPTN 037 (HPTN); HPTN035 (MTCT); and HVTN (502) as a component of this application. The research team of the PENN Prevention CTU includes investigators with a long history of collaboration and scientific contribution at the local, national and international level. Investigators have served in leadership positions on the HIVNET Scientific Steering Committee (member), the HPTN Protocol Review Committee (member), and the HPTN Substance Use Working Group (Chair). Our site is listed as a preferred site in each of the three networks with which we seek Investigators are also listed key personnel in two of the proposed leadership group applications (Microbicides and HPTN). The PENN Prevention CTU will be fully integrated with the PENN Therapeutics CTU (ACTG) and the CHOP CTU (IMPACT). We will expand our current collaborations with investigators from these CTUs and have developed organizational structures that will result in efficiencies across Networks and CTUs including the use of shared laboratory, pharmacy, training, and QA/QC resources. A Scientific Advisory Board will connect our CTUs to the scientific expertise available on campus. The HIV epidemic in Philadelphia provides an important opportunity to conduct prevention science. Our site continues to develop strategies designed to access high risk populations necessary to contribute to the completion of the proposed scientific agendas of the three networks. We are proposing a Clinical Research Site in the Ukraine where the study team has an impressive record of recruiting high incidence cohorts. The Prevention Community Advisory Board (CAB) has been meeting on a monthly basis since 1993. Members of this CAB have a long history of participation in prevention research through the conduct of community and participant education initiatives and service on numerous protocol teams.